Substituting dexamethasone for prednisone complicates remission induction in children with acute lymphoblastic leukemia.

BACKGROUND: The authors report the occurrence of fatal or near-fatal sepsis in 16 of 38 children with newly diagnosed acute lymphoblastic leukemia (ALL) treated with a new induction regimen that differed from its predecessor by the substitution of dexamethasone for prednisone. METHODS: The frequency of septic deaths among 38 children who received multiagent remission induction therapy, including dexamethasone (6 mg/m(2)) daily for 28 days (pilot protocol 91-01P), was compared with the frequency of septic deaths among children previously treated (protocol 87-01) and subsequently treated (protocol 91-01) in consecutive Dana-Farber Cancer Institute (DFCI) ALL trials with induction therapy that included 21 and 28 days of prednisone (40 mg/m(2)), respectively. Except for dexamethasone in protocol 91-01P, the remission induction agents used were identical in substance to those used in protocol 87-01. Protocol 91-01, the successor 91-01P, was also similar, with the exception of the deletion of a single dose of L-asparaginase. RESULTS: Sixteen of the 38 children (42%) treated on the DFCI 91-01P had documented gram positive or gram negative sepsis (17 episodes) during remission induction, including 4 toxic deaths (11%). In contrast, there were 4 induction deaths among 369 children (1%) treated on protocol 87-01 (P = 0.0035) and 1 induction death among 377 children (<1%) treated on protocol 91-01 (P = 0.0003). CONCLUSIONS: Substitution of dexamethasone for prednisone or methylprednisolone in an otherwise intensive conventional induction regimen for previously untreated children with ALL resulted in an alarmingly high incidence of septic episodes and toxic deaths. Awareness of this complication, considering that the substitution has no apparent benefit in the efficacy of remission induction, argues against its routine use in intensive induction regimens for children with ALL.

Advance directives: barriers to completion.

The concept of advance directives, although sound in theory, appears to be failing to meet the needs of many patients. Advance directives have been endorsed by both the healthcare profession and the general public, yet few individuals have documented their wishes for treatment preferences in end-of-life decisions. A review of 15 research articles revealed three main barriers to the completion and effective use of advance directives. These barriers are: (a) lack of education or knowledge regarding advance directives, (b) difficulties with paperwork completion, and (c) discordance between patient, family members or proxy, and provider. Future research is suggested to generate information that will facilitate meeting the needs of patients and their families in this most difficult aspect of healthcare delivery.

Color management of cosmetic restorations.

Ideally, a cosmetic restoration should be indistinguishable from the surrounding unrestored dentition. The cosmetic dentist faces the challenging task of creating the restoration using materials that do not possess the light-transmitting properties of natural tooth structures. A thorough knowledge of the physical and physiologic properties of light, color production and perception, and skill in the art of color matching can lead to rewarding success.

A prospective trial of colchicine for primary biliary cirrhosis.

We entered 60 patients with primary biliary cirrhosis in a double-blind randomized controlled trial to determine whether colchicine is therapeutically effective. Thirty patients had early disease (Stages 1 and 2), and 30 had advanced disease (Stages 3 and 4). Fifteen patients with early disease and 15 with advanced disease received colchicine (0.6 mg twice daily), and the remainder received placebo. Patients were studied about every two months; those remaining in the blind phase at two years underwent repeat liver biopsy and were then placed on open-label colchicine (0.6 mg twice daily). With a few exceptions, the results in patients with early disease were similar to those in patients with advanced disease; hence, data on patients in all stages were combined in the main analysis. During the two-year study period the colchicine-treated patients, as compared with the placebo-treated patients, had improvement in levels of serum albumin, serum bilirubin, alkaline phosphatase, cholesterol, and aminotransferases. However, there was no such improvement in the severity of symptoms or physical findings; moreover, there was no significant difference in the histologic changes noted at liver biopsy in the two treatment groups. At four years after entry, the cumulative mortality from liver disease was 21 percent in patients given colchicine and 47 percent in those given placebo (P = 0.05). The only side effect of colchicine was diarrhea, noted in three patients. The consistent and significant improvement in a number of markers of liver disease and the apparent decreased mortality from liver disease suggest that colchicine may provide some long-term clinical benefit in patients with primary biliary cirrhosis. However, the failure of colchicine to reduce hepatic inflammation and fibrosis leaves uncertain the effect of the drug on the longterm outcome of this disease.

The effect of heart rate on in utero left ventricular output in the fetal sheep.

The effect of heart rate on left ventricular output was examined in seven fetal lambs at ages of 128 to 140 gestational days. The fetuses had been surgically instrumented at least 4 days previously with an ascending aortic flow probe, left ventricular dimension transducers, and left and right atrial pacing electrodes. Natural variations in heart rate of the lambs taken as a group correlated positively with left ventricular output, and negatively with ventricular end-diastolic dimension and stroke volume (P less than 0.0001). Rate did not affect output with right atrial pacing. With left atrial pacing, it correlated negatively with output (P less than 0.0001). At both pacing sites, rate correlated negatively with end-diastolic dimension and stroke volume (P less than 0.0001). The introduction of a longer interval during each pacing rate circumvented the rate-related changes in dimension and allowed the ventricle to fill to the same end-diastolic dimension. The systole at the end of the longer interval had a greater stroke volume than the preceding systoles. The faster the preceding paced rate, the greater was the stroke volume (P less than 0.0001). This study demonstrates that experimentally induced variations in heart rate produce changes in end-diastolic volume and contractility which prominently affect stroke volume. Over a broad range of rates, however, the effect of rate on left ventricular output is either negative or absent. With naturally occurring rate changes, there are additional changes in contractility and venous return which affect stroke volume. These combine to produce a positive relation between heart rate and left ventricular output. These effects of heart rate on output are qualitatively similar to those described for the adult animal.

An in vivo strain gage study of elongation of the anterior cruciate ligament.

The purpose of this paper is to study the load-elongation characteristics of a Grade II sprain of the anterior cruciate ligament (ACL) at the time of local anesthesia arthroscopy. The data may be used to increase diagnostic and prognostic accuracy when evaluating Grade II ACL sprains and to structure properly a rehabilitation program following ACL injury. This report is based on the data from two in vivo strain gage studies of Grade II ACL sprains. Following instrumentation of the ligament, several events common to physical examination and rehabilitation programs were tested. The Lachman test produced greater elongation of the anteromedial fibers than did the anterior drawer or pivot shift test. A fairly high force of 80 pounds may be required by the examiner's hands to test satisfactorily the anteromedial fibers in the acutely injured large athlete. The proper order for a rehabilitation program should be crutch walking, cycling, walking, slow running, and faster running. Patients should be cautioned to run on a perfectly level surface. Cycling produced 7% as much elongation as an 80 pound Lachman test, and the one leg half squat 21% as much. Quadriceps rehabilitation can be done more safely using these exercises. Quadriceps exercises by knee extension against a 20 pound weight boot in the range of full extension to 22 degrees flexion created peak elongation of the anteromedial fibers ranging from 87 to 121% of that produced by an 80 pound Lachman test. We recommend that quadriceps exercises and testing by knee extension through a full range of motion not be done during the first year following ACL injury or reconstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Developmental changes in cardiac contractility in fetal and postnatal sheep: in vitro and in vivo.

Developmental changes in contractility were sought in the fetal and postnatal sheep heart by using postextrasystolic potentiation and force, pressure, and wall-motion measures. Two different preparations were used, isolated myocardium and the chronically instrumented lamb. In the isolated muscle, the following increased significantly with age: force of contraction, the maximum rate of rise of force, and postextrasystolic potentiation. In the intact heart prior to birth [period of study, 20 +/- 4 (SD) days] heart rate (HR) fell significantly, and the following increased significantly: postextrasystolic potentiation [measured with the maximum rate of rise of left ventricular (LV) pressure (Pmax)], LV peak systolic pressure (LVP), end-diastolic dimension (EDD), end-systolic dimension (ESD), and aortic diastolic pressure. After birth, LVP, Pmax, HR, LVEDP, EDD, and ESD increased and postextrasystolic potentiation fell. The latter fall was not found in vitro and probably demonstrates a transient change in contractility, related to hormonal or neural stimulation. Over the subsequent postnatal days (6-122 days), HR fell while potentiation, EDD, and ESD increased significantly. Both in vitro and in vivo, the overall increase in postextrasystolic potentiation demonstrates a similar long-term change in contractility. The similarity of this change to that induced by mild hypertrophy suggests that development and mild hypertrophy alter myocardial contractility through a common mechanism.

Automatic tachycardia recognition.

A microcomputer algorithm for tachycardia identification, suitable for use in an implanted antitachycardia pacemaker, is described. The system employs an atrial and ventricular electrogram, detects a sustained fast rate in either chamber, and awakens the main program to perform detailed analysis of the tachycardia and its immediately preceding beats. The algorithm distinguishes atrial, ventricular, and AV nodal and re-entrant tachycardia from high rates due to sinus tachycardia. For testing of the program, we used a data base of twenty-two tape-recorded and documented arrhythmias provoked during electrophysiologic studies in which atrial and ventricular bipolar electrodes were in place; twenty-one were successfully detected. These included atrial fibrillation, atrial flutter, atrial tachycardia, AV nodal re-entrant tachycardia, AV re-entrant tachycardia using an accessory pathway, and ventricular tachycardia with and without ventriculo-atrial conduction.

Biophysics of the developing heart. III. A comparison of the left ventricular dynamics of the fetal and neonatal lamb heart.

Changes in heart rate, left ventricular dimensions, and inotropic state of chronically instrumented lambs from in utero to neonatal life are described and analyzed. Six lambs were instrumented from 5 to 23 days prior to parturition and studied prior to and after birth. Heart rate, aortic systolic and diastolic pressure, left ventricular end-diastolic and peak systolic pressure, and left ventricular minor axis end-diastolic (EDD) and end-systolic dimension (ESD) were monitored. The maximum rate of rise of left ventricular pressure (Pmax), percentage fractional shortening [(EDD - ESD divided by EDD) x 100%; %FS], and the Pmax -interval ratio (this ratio of Pmax of the postextrasystolic potentiated systole to Pmax of the previous regular systole is independent of volume) described contractility. Subsequent to birth: heart rate, aortic systolic and diastolic pressure and left ventricular dimensions increased; during spontaneous rhythm and at equal fetal and neonatal heart rates and ventricular dimensions, %FS and P max increased significantly; and P max -interval ratio changed significantly. An increase in myocardial inotropic state occurs with birth. This enhancement is in addition to the effects of the increase in heart rate and end-diastolic volume that occur with the adaptation to birth.

Uridine diphosphate glucose-sterol glucosyltransferase and nucleoside diphosphatase activities in etiolated pea seedlings.

1. UDP-glucose-sterol glucosyltransferase and nucleoside diphosphatases were isolated in a particulate fraction from 7-day-old etiolated pea seedlings. The glucosyltransferase and UDPase (uridine diphosphatase) are stimulated by Ca2+ cation, less so by Mg2+ cation, and inhibited by Zn2+. 2. Each activity has a pH optimum near 8. 3. The glucosyltransferase is specific for UDP-glucose as the glucosyl donor and is inhibited by UDP. Partial recovery from UDP inhibition is effected by preincubation of the enzyme. 4. Freeze-thaw treatment and subsequent sucrose-density-gradient centrifugation of the particulate fraction shows the glucosyltransferase to be widely distributed among cell fractions but to be most active in particles with a density of 1.15 g/ml. UDPase is most active in particulate material with a density of over 1.18 g/ml but an activity peak also appears at 1.15 g/ml. Of several nucleoside diphosphatase activities, UDPase activity is most enhanced by the freeze-thaw and sucrose-density-gradient-fractionation procedures. 5. Detergent treatment with 0.1% sodium deoxycholate allows the partial solubilization of the glucosyltransferase and UDPase. The two activities are similarly distributed between pellet and supernatant after high-speed centrifugation for two different time intervals. 6. A role for UDPase in the functioning of glucosylation reactions is discussed.